CN112175150A - Novel preparation method of functionalized porous magnetic microspheres - Google Patents
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Abstract
The invention provides a novel preparation method of functionalized porous magnetic microspheres, which comprises the following steps of firstly preparing seed microspheres with uniform particle size through polymerization reaction; secondly, preparing porous microspheres with functional groups on the surfaces by adopting a seed polymerization method, and thirdly, modifying the porous microspheres to charge the surfaces; then preparing surface-charged or surface-hydrophilic-hydrophobic magnetic nanoparticles with controllable particle size, mixing the surface-modified porous microspheres with the surface-charged or surface-hydrophilic-hydrophobic magnetic nanoparticles, adjusting the pH value to ensure that the surface charges of the porous microspheres are opposite to those of the magnetic nanoparticles, adsorbing a layer of magnetic nanoparticles in porous microsphere pore channels through electrostatic action, and then synthesizing a functionalized shell layer on the surfaces of the porous magnetic microspheres to prepare the functionalized porous magnetic microspheres; the functionalized porous magnetic microsphere prepared by the method has the characteristics of uniform particle size, consistent magnetic content and rich surface functional groups.
Description
Technical Field
The invention belongs to the field of material chemical industry, and particularly relates to a novel preparation method of a functionalized porous magnetic microsphere.
Background
The magnetic microsphere is a novel nano material, is the most widely cited core raw material in the field of in vitro diagnosis, and is a spherical magnetic material with the grain diameter of about several hundred nanometers to several micrometers, which is formed by combining an inorganic magnetic material and an organic polymer, on one hand, functional groups can be introduced into the surface of the magnetic microsphere, and the magnetic microsphere is coupled with antibodies, antigens or other biomolecules, and the quantitative analysis of a target object is realized by an immunoreaction and a high-sensitivity detection means; on the other hand, because the magnetic microspheres have convenient magnetic field control characteristics, when the magnetic microspheres are used as carriers to replace the traditional multi-well plate or other solid phase carriers, and are combined with various immunoassay signal marking means (such as immunoassay labeling methods such as enzyme-linked immunosorbent assay, chemiluminescence assay, fluorescence assay or immunoassay PCR assay) to realize rapid, automatic and multi-flux assay. Therefore, for the magnetic microspheres of the carrier or the signal marking material applied to in vitro separation and disease diagnosis, the magnetic microspheres have the characteristics of good spherical homogeneous structure, higher specific saturation magnetization, abundant functional groups on the surface, good biocompatibility, dispersion stability, lower non-specific adsorption property and the like, so that the sensitivity and consistency of detection can be ensured.
Currently, the preparation methods of magnetic microspheres mainly include a polymer embedding method, a monomer polymerization method, an interfacial deposition method, an in-situ method, preparation of inorganic magnetic carriers, and the like, in which the monomer polymerization method is most applied, including an emulsion polymerization method, a dispersion polymerization method, a suspension polymerization method, a seed polymerization method, and the like, and the key problem to be solved in the monomer polymerization method is the compatibility between inorganic magnetic nanoparticles and organic vinyl monomers. Except for seed polymerization, most of the magnetic microspheres prepared by other methods have the defects of uneven particle size distribution, low magnetic content, few surface functional groups and the like. The seed polymerization method has the advantages of uniform particle size distribution, uniform magnetic content, rich surface functional groups and the like, and is a main production method of the magnetic microspheres at present. Most of magnetic microspheres prepared based on a seed polymerization method are porous structures, ferric chloride or ferrous chloride solution is used for soaking the porous microspheres, then ammonia water is used as a reducing agent for reduction, ferric ions and ferrous ions are reduced into ferric oxide or ferroferric oxide, the ferric oxide or the ferroferric oxide is deposited in pore channels, and the outer layer is wrapped by a functional polymer. The magnetic microsphere prepared by the method has the advantages that large magnetic core aggregates are easily adsorbed on the surface and are not easy to remove, so that the surface is covered and cannot be coated by a functional group shell layer, and the reduction of surface functional groups is caused, so that the problems of large measurement error, high background value, low sensitivity and the like caused by non-specific adsorption are easily caused in the use process. Therefore, it is imperative to develop a novel method for preparing magnetic microspheres, which has uniform particle size distribution, uniform magnetic content and abundant surface functional groups.
Disclosure of Invention
In order to solve the problems, the invention discloses a novel preparation method of a functionalized porous magnetic microsphere, which effectively solves the problems of magnetic nucleus aggregation on the surface, uneven surface hydrophilicity and hydrophobicity, less functional groups and the like in the preparation process of the magnetic microsphere.
In order to achieve the above purpose, the invention provides the following technical scheme:
(1) preparing seed microspheres;
(2) preparing the seed microspheres by a seed polymerization method to obtain porous microspheres;
(3) carrying out surface modification on the porous microspheres to obtain modified porous microspheres;
(4) mixing the modified porous microspheres and the surface functionalized magnetic nanoparticles, adjusting the pH of the mixed solution, and uniformly adsorbing the surface functionalized magnetic nanoparticles in the pore channels of the modified porous microspheres by using electrostatic action to obtain porous magnetic microspheres;
(5) and reacting allyl glycidyl ether with the porous magnetic microspheres to obtain pre-coated porous magnetic microspheres, and adding the functional monomer 2 to polymerize to obtain the functionalized porous magnetic microspheres.
Further, the preparation process of the porous microspheres in the step (2) is as follows: adding an emulsifier and a stabilizer into water, and stirring and dissolving to obtain a solution A; mixing the functional monomer 1, a pore-forming agent and an initiator, and stirring for dissolving to obtain a solution B; adding the solution B into the solution A, emulsifying for 10-30 min under stirring at 2000-7000 rpm, adding the seed microspheres prepared in the step (1), and continuing to emulsify for 10-60 min; heating to 30-60 ℃, and reacting for 24 hours under the stirring of 200-500 rpm; adjusting the rotating speed to be 100-500 rpm, heating to 60-80 ℃, stirring for 2 hours, continuously heating to 70-90 ℃, and stirring for 24 hours to obtain the porous microspheres.
Further, the functional monomer 1 is one of styrene, methacrylic acid, glycidyl methacrylate, methyl acrylate, ethyl acrylate and acrylic acid; the initiator is one of AIBN, BPO and KPS; the emulsifier is one of sodium dodecyl sulfate and sodium dodecyl benzene sulfonate; the pore-foaming agent is one or more of toluene, cyclohexanol and n-octanol; the stabilizer is one of PVP-K30 and PVA.
Further, the mass ratio of the functional monomer 1 to the seed microspheres is 1-10: 1; the dosage of the initiator is 0.01 to 1 percent of the total volume of the solution A and the solution B; the dosage of the emulsifier is 0.1-2% of the total volume of the solution A and the solution B; the dosage of the pore-foaming agent is 0.1-10% of the total volume of the solution A and the solution B; the dosage of the stabilizer is 0.1-2% of the total volume of the solution A and the solution B.
Further, the preparation process of the surface functionalized magnetic nanoparticles in the step (4) comprises the following steps: taking ferric chloride hydrate and ferrous chloride hydrate as raw materials, adding a reducing agent, and simultaneously adding a surface functional group compound to prepare surface functionalized magnetic nanoparticles with a large amount of charges on the surface or different surface hydrophilicity and hydrophobicity; the mass ratio of the ferric chloride hydrate to the modified porous microspheres is 0.5-10: 1; the mass ratio of the ferrous chloride hydrate to the modified porous microspheres is 0.5-10: 1; the mass ratio of the reducing agent to the ferric chloride hydrate is 0.1-10: 1; the mass ratio of the surface functional group compound to the modified porous microspheres is 0.5-10: 1.
Further, the surface functional group compound is one of citric acid, polyethylene glycol and oleic acid; the particle size of the surface functionalized magnetic nanoparticles is 5-200 nanometers.
Further, the mass ratio of the modified porous microspheres to the surface functionalized magnetic nanoparticles in the step (4) is 1: 1 to 10.
Further, in the step (4), the pH value of the mixed solution is adjusted to 2.0-9.0.
Further, the seed microsphere in the step (1) is one of a polystyrene microsphere, a polyglycidyl methacrylate microsphere, a polymethyl methacrylate microsphere, an agarose microsphere, a dextran microsphere and a chitosan microsphere; preferably, the seed microsphere is one of polystyrene microsphere, polymethyl methacrylate microsphere and polyglycidyl methacrylate microsphere, and the preparation method of the seed microsphere in the step (1) is one of dispersion polymerization method, emulsion polymerization method, soap-free emulsion polymerization method and miniemulsion polymerization method; the particle size of the seed microspheres in the step (1) is 0.1-5 microns.
Further, the functional monomer 2 in the step (5) is one of acrylic acid, methacrylic acid, glycidyl methacrylate, methyl acrylate and ethyl acrylate; in the step (5), the mass ratio of the functional monomer 2 to the porous magnetic microspheres is 1-10: 1; the mass ratio of the allyl glycidyl ether to the porous magnetic microspheres in the step (5) is 1-10: 1.
compared with the prior art, the invention has the following advantages and beneficial effects:
(1) according to the method, the seed microspheres and the functional monomers are polymerized to prepare the porous microspheres, the functional monomers are different from the seed microsphere monomers, so that the porous microspheres are of a shell-core structure, and the shell layers are full of pore channels, so that the surface area of the microspheres can be increased, the adsorption capacity of magnetic nanoparticles can be increased, the magnetic response performance can be improved, and the surface functional group modification content can be improved.
(2) According to the invention, the surface of the porous microsphere is modified, the surface functionalized magnetic nanoparticles are prepared, the surface of the porous microsphere is provided with different charges, electrostatic magnetization is realized through simple pH adjustment, the charged magnetic nanoparticles are uniformly adsorbed in the pore channel of the porous microsphere, and the magnetic response performance and the suspension performance of the magnetic microsphere in a solution can be adjusted.
(3) The functionalized porous magnetic microsphere prepared by the invention has the advantages of uniform particle size distribution, uniform magnetic content, rich surface functional groups and good application prospect.
Drawings
FIG. 1 is a scanning electron microscope image of a polystyrene seed microsphere prepared in example 1 of the present invention;
FIG. 2 is a scanning electron microscope image of a PST @ PGMA porous microsphere prepared in example 1 of the present invention;
FIG. 3 is a scanning electron microscope image of the functionalized porous magnetic microsphere prepared in example 1 of the present invention.
Detailed Description
The technical solutions provided by the present invention will be described in detail below with reference to specific examples, and it should be understood that the following specific embodiments are only illustrative of the present invention and are not intended to limit the scope of the present invention.
Example 1
(1) Preparation of seed microspheres, in this example, soap-free emulsion polymerization was used to prepare polystyrene microspheres. The specific synthesis method comprises the following steps:
1) adding 500mL of deionized water and 50mL of styrene into a 1L three-necked bottle, introducing nitrogen at room temperature, stirring for 10 minutes, and rotating at the speed of 200 rpm;
2) adding 1.0g of potassium persulfate into 50mL of deionized water, and dissolving by ultrasonic waves;
3) the potassium persulfate solution was poured into (1), heated to 80 ℃ and stirred at 200rpm for 24 hours.
The scanning electron micrograph of the prepared styrene seed microsphere is shown in figure 1, and the particle size of the seed microsphere is 700 nanometers.
(2) In this embodiment, glycidyl methacrylate is used as a functional monomer, cyclohexanol is used as a pore-forming agent, SDS is used as an emulsifier, PVP-K30 is used as a stabilizer, and BPO is used as an initiator to prepare the porous microsphere, and the specific method is as follows:
1) weighing 2.15g of SDS and 1.08g of PVP-K30 in water, preparing 200mL of solution, and stirring for dissolving to obtain solution A;
2) mixing 5mLGMA, 10mL of cyclohexanol and 0.2g of BPO, and stirring to dissolve to obtain a solution B;
3) adding the solution B into the solution A completely, emulsifying for 30min under stirring at 5000rpm, adding PST seed microspheres 5.37g, continuing to emulsify for 30min, introducing into a three-necked bottle, stirring for 24 h at 40 ℃, and stirring at 200 rpm; adjusting the rotation speed to 150rpm, heating to 60 deg.C, stirring for 2 hr, heating to 70 deg.C, stirring for 24 hr to obtain porous microsphere with uniform surface particle diameter, wherein the particle diameter is 1 μm, and the scanning electron microscope image of PST @ PGMA porous microsphere is shown in FIG. 2.
(3) And (3) preparing the modified porous microspheres, namely taking the PST @ PGMA porous microspheres prepared in the step (2), centrifugally washing the PST @ PGMA porous microspheres for 5 times by using deionized water, adding ethylenediamine with the mass being 2 times of that of the porous microspheres, and stirring the mixture for 24 hours at 80 ℃ to obtain the PST @ PGMA modified porous microspheres.
(4) The preparation of the surface functionalized magnetic nanoparticles, in this example, a coprecipitation method is adopted, and the specific synthesis steps are as follows:
adding 30.6g of ferric chloride hexahydrate into 475mL of deionized water, introducing nitrogen, stirring for dissolving, adding 11.5g of ferrous chloride tetrahydrate, heating to 90 ℃, adjusting the stirring speed to 300rpm, rapidly adding 36mL of ammonia water, stirring for 5 minutes, adding 56g of citric acid, stirring for 2 hours at 90 ℃, cooling to room temperature, enabling the magnet to be adsorbed, and adding deionized water for repeatedly washing for 6 times. Obtaining the citric acid modified magnetic nano-particles with a large amount of negative charges on the surface.
(5) The preparation of the porous magnetic microsphere adopts a method for mixing the modified porous microsphere and the charged magnetic nanoparticles, and the specific implementation process is as follows:
adding 11.2g of modified porous microspheres into 112mL of deionized water, performing ultrasonic dispersion, adjusting the pH to be less than 4.0 by using hydrochloric acid, adding 56g of citric acid modified magnetic nanoparticles, performing vibration adsorption for 2 hours, performing centrifugal separation, removing the non-adsorbed magnetic nanoparticles on the upper layer, and repeatedly washing with deionized water for 6 times to obtain the porous magnetic microspheres with the magnetic nanoparticles adsorbed on the surfaces.
(6) The preparation of the surface functionalized magnetic microsphere comprises the step of polymerizing the surface of the porous magnetic microsphere with the surface adsorbed with the magnetic nano particles as a core and acrylic acid as a functional monomer to obtain the surface modified carboxyl functionalized porous magnetic microsphere. In this example, a dispersion polymerization method is used, and the specific implementation method is as follows:
1) weighing 1g of porous magnetic microspheres, adding 6.7mL of diethylene glycol dimethyl ether, adding 2g of allyl glycidyl ether, and stirring at 80 ℃ for 18 hours;
2) after completion of the previous reaction step, 5 washes with methanol, methanol/isopropanol = 3: 7 washing the mixed solution for 3 times, dispersing the porous magnetic microspheres by using the mixed solution, adjusting the concentration to 15w/v%, adding 0.14g of AIBN, adding 5g of acrylic acid, and reacting for 24 hours at 75 ℃ to obtain the functionalized porous magnetic microspheres, wherein a scanning electron microscope image is shown in figure 3.
Example 2
(1) Preparation of seed microspheres, in this example, the poly glycidyl methacrylate microspheres were prepared by soap-free emulsion polymerization. The specific synthesis method comprises the following steps:
1) adding 600mL of deionized water and 30mL of glycidyl methacrylate into a 1L three-necked bottle, introducing nitrogen at room temperature, stirring for 10 minutes, and rotating at the speed of 200 rpm;
2) adding 0.8g of potassium persulfate into 36mL of deionized water, and dissolving by ultrasonic waves;
3) the potassium persulfate solution was poured into (1), heated to 75 ℃ and stirred at 200rpm for 24 hours.
(2) In this embodiment, methyl acrylate is used as a functional monomer, n-octanol is used as a pore-forming agent, SDS is used as an emulsifier, PVP-K30 is used as a stabilizer, and AIBN is used as an initiator to prepare the porous microsphere, and the specific method is as follows:
1) weighing 2g of SDS and 1.2g of PVP-K30 in water, preparing 200mL of solution, and stirring for dissolving to obtain solution A;
2) 5mL of methyl acrylate, 10mL of n-octanol and 0.2g of AIBN are mixed and stirred to be dissolved to obtain a solution B;
3) adding the solution B into the solution A completely, emulsifying for 30min under stirring at 5000rpm, adding 5.0g of poly glycidyl methacrylate seed microspheres, continuing to emulsify for 30min, introducing into a three-necked bottle, stirring for 24 h at 40 ℃, and stirring at 200 rpm; regulating the rotating speed to 150rpm, heating to 60 ℃, stirring for 2 hours, continuously heating to 70 ℃, and stirring for 24 hours to obtain the porous microspheres with uniform surface grain sizes.
(3) And (3) preparing modified porous microspheres, namely taking the porous microspheres prepared in the step (2), centrifugally washing the porous microspheres for 5 times by using deionized water, adding ethylenediamine with the mass being 2 times of that of the porous microspheres, and stirring the mixture for 24 hours at 80 ℃ to obtain the modified porous microspheres.
(4) The preparation of the surface functionalized magnetic nanoparticles, in this example, a coprecipitation method is adopted, and the specific synthesis steps are as follows:
adding 32g of ferric chloride hexahydrate into 500mL of deionized water, introducing nitrogen, stirring for dissolving, adding 12g of ferrous chloride tetrahydrate, heating to 90 ℃, adjusting the stirring speed to 300rpm, rapidly adding 48mL of ammonia water, stirring for 5 minutes, adding 48g of citric acid, stirring for 2 hours at 90 ℃, cooling to room temperature, enabling the magnet to be adsorbed, and adding deionized water for repeatedly washing for 6 times. Obtaining the citric acid modified magnetic nano-particles with a large amount of negative charges on the surface.
(5) The preparation of the porous magnetic microsphere adopts a method for mixing the modified porous microsphere and the charged magnetic nanoparticles, and the specific implementation process is as follows:
adding 15g of modified porous microspheres into 150mL of deionized water, performing ultrasonic dispersion, adjusting the pH to be less than 3.0 by using hydrochloric acid, adding 48g of citric acid modified magnetic nanoparticles, performing vibration adsorption for 2 hours, performing centrifugal separation, removing the non-adsorbed magnetic nanoparticles on the upper layer, and repeatedly washing with deionized water for 6 times to obtain the porous magnetic microspheres with the magnetic nanoparticles adsorbed on the surfaces.
(6) The preparation of the surface functionalized magnetic microsphere comprises the step of polymerizing the surface of the porous magnetic microsphere with the surface adsorbed with the magnetic nano particles as a core and acrylic acid as a functional monomer to obtain the surface modified carboxyl functionalized porous magnetic microsphere. In this example, a dispersion polymerization method is used, and the specific implementation method is as follows:
1) weighing 1g of porous magnetic microspheres, adding 5mL of diethylene glycol dimethyl ether, adding 5g of allyl glycidyl ether, and stirring at 80 ℃ for 18 hours;
2) after completion of the previous reaction step, 5 washes with methanol, methanol/isopropanol = 4: and 6, washing the mixture for 3 times, dispersing the porous magnetic microspheres by using the mixture, adjusting the concentration to 15w/v%, adding 0.15g of AIBN, adding 10g of acrylic acid, and reacting for 24 hours at 75 ℃ to obtain the functionalized porous magnetic microspheres.
Example 3
(1) Preparation of seed microspheres, in this example, soap-free emulsion polymerization was used to prepare polystyrene microspheres. The specific synthesis method comprises the following steps:
1) adding 500mL of deionized water and 50mL of styrene into a 1L three-necked bottle, introducing nitrogen at room temperature, stirring for 10 minutes, and rotating at the speed of 200 rpm;
2) adding 1.0g of potassium persulfate into 50mL of deionized water, and dissolving by ultrasonic waves;
3) the potassium persulfate solution was poured into (1), heated to 80 ℃ and stirred at 200rpm for 24 hours.
(2) In this embodiment, glycidyl methacrylate is used as a functional monomer, cyclohexanol is used as a pore-forming agent, SDS is used as an emulsifier, PVP-K30 is used as a stabilizer, and BPO is used as an initiator to prepare the porous microsphere, and the specific method is as follows:
1) weighing 0.23g of SDS and 2g of PVP-K30 in water, preparing 200mL of solution, and stirring for dissolving to obtain solution A;
2) mixing 10mLGMA, 20mL cyclohexanol and 0.1g AIBN, and stirring to dissolve to obtain solution B;
3) adding the solution B into the solution A completely, emulsifying for 30min under stirring at 5000rpm, adding 5.37g of PST seed microspheres, continuing to emulsify for 30min, introducing into a three-necked bottle, and stirring for 24 hours at 40 ℃ at 200 rpm; regulating the rotating speed to 150rpm, heating to 60 ℃, stirring for 2 hours, continuously heating to 70 ℃, and stirring for 24 hours to obtain the porous microspheres with uniform surface grain sizes.
(3) And (3) preparing the modified porous microspheres, namely taking the PST @ PGMA porous microspheres prepared in the step (2), centrifugally washing the PST @ PGMA porous microspheres for 5 times by using deionized water, adding ethylenediamine with the mass being 2 times of that of the porous microspheres, and stirring the mixture for 24 hours at 80 ℃ to obtain the PST @ PGMA modified porous microspheres.
(4) The preparation of the surface functionalized magnetic nanoparticles, in this example, a coprecipitation method is adopted, and the specific synthesis steps are as follows:
adding 35g of ferric chloride hexahydrate into 500mL of deionized water, introducing nitrogen, stirring for dissolving, adding 15g of ferrous chloride tetrahydrate, heating to 90 ℃, adjusting the stirring speed to 600rpm, rapidly adding 50mL of ammonia water, stirring for 5 minutes, adding 36g of citric acid, stirring for 2 hours at 90 ℃, cooling to room temperature, enabling the magnet to be adsorbed, and adding deionized water for repeatedly washing for 6 times. Obtaining the citric acid modified magnetic nano-particles with a large amount of negative charges on the surface.
(5) The preparation of the porous magnetic microsphere adopts a method for mixing the modified porous microsphere and the charged magnetic nanoparticles, and the specific implementation process is as follows:
adding 10g of modified porous microspheres into 200mL of deionized water, performing ultrasonic dispersion, adjusting the pH to be less than 4.0 by using hydrochloric acid, adding 20g of citric acid modified magnetic nanoparticles, performing vibration adsorption for 2 hours, performing centrifugal separation, removing the non-adsorbed magnetic nanoparticles on the upper layer, and repeatedly washing with deionized water for 6 times to obtain the porous magnetic microspheres with the magnetic nanoparticles adsorbed on the surfaces.
(6) The preparation of the surface functionalized magnetic microsphere comprises the step of polymerizing the surface of the porous magnetic microsphere with the surface adsorbed with the magnetic nano particles as a core and acrylic acid as a functional monomer to obtain the surface modified carboxyl functionalized porous magnetic microsphere. In this example, a dispersion polymerization method is used, and the specific implementation method is as follows:
1) weighing 1g of porous magnetic microspheres, adding 10mL of diethylene glycol dimethyl ether, adding 1g of allyl glycidyl ether, and stirring at 80 ℃ for 18 hours;
2) after completion of the previous reaction step, 5 washes with methanol, methanol/isopropanol = 3: 7 washing the mixed solution for 3 times, dispersing the porous magnetic microspheres by using the mixed solution, adjusting the concentration to 10w/v%, adding 0.1g of AIBN, adding 2g of acrylic acid, and reacting for 24 hours at 75 ℃ to obtain the functionalized porous magnetic microspheres.
The technical means disclosed in the invention scheme are not limited to the technical means disclosed in the above embodiments, but also include the technical scheme formed by any combination of the above technical features. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and such improvements and modifications are also considered to be within the scope of the present invention.
Claims (10)
1. A novel preparation method of functionalized porous magnetic microspheres is characterized by comprising the following steps:
(1) preparing seed microspheres;
(2) preparing the seed microspheres into porous microspheres by a seed polymerization method;
(3) carrying out surface modification on the porous microspheres to obtain modified porous microspheres;
(4) mixing the modified porous microspheres with the surface functionalized magnetic nanoparticles, and adjusting the pH of the mixed solution to obtain porous magnetic microspheres;
(5) and reacting allyl glycidyl ether with the porous magnetic microspheres to obtain pre-coated porous magnetic microspheres, and adding the functional monomer 2 to polymerize to obtain the functionalized porous magnetic microspheres.
2. The novel method for preparing functionalized porous magnetic microspheres according to claim 1, wherein the porous microspheres prepared in step (2) are prepared by the following steps: adding an emulsifier and a stabilizer into water, and stirring and dissolving to obtain a solution A; mixing the functional monomer 1, a pore-forming agent and an initiator, and stirring for dissolving to obtain a solution B; adding the solution B into the solution A, emulsifying for 10-30 min under stirring at 2000-7000 rpm, adding the seed microspheres prepared in the step (1), and continuing to emulsify for 10-60 min; heating to 30-60 ℃, and reacting for 24 hours under the stirring of 200-500 rpm; adjusting the rotating speed to be 100-500 rpm, heating to 60-80 ℃, stirring for 2 hours, continuously heating to 70-90 ℃, and stirring for 24 hours to obtain the porous microspheres.
3. The novel preparation method of the functionalized porous magnetic microsphere according to claim 2, wherein the functional monomer 1 is one of styrene, methacrylic acid, glycidyl methacrylate, methyl acrylate, ethyl acrylate and acrylic acid; the initiator is one of AIBN, BPO and KPS; the emulsifier is one of sodium dodecyl sulfate and sodium dodecyl benzene sulfonate; the pore-foaming agent is one or more of toluene, cyclohexanol and n-octanol; the stabilizer is one of PVP-K30 and PVA.
4. The novel preparation method of the functionalized porous magnetic microsphere according to claim 2, wherein the mass ratio of the functional monomer 1 to the seed microsphere is 1-10: 1; the dosage of the initiator is 0.01 to 1 percent of the total volume of the solution A and the solution B; the dosage of the emulsifier is 0.1-2% of the total volume of the solution A and the solution B; the dosage of the pore-foaming agent is 0.1-10% of the total volume of the solution A and the solution B; the dosage of the stabilizer is 0.1-2% of the total volume of the solution A and the solution B.
5. The novel preparation method of the functionalized porous magnetic microsphere according to claim 1, wherein the preparation process of the surface functionalized magnetic nanoparticles in the step (4) is as follows: mixing ferric chloride hydrate, ferrous chloride hydrate, a reducing agent and a surface functional group compound to obtain surface functionalized magnetic nanoparticles; the mass ratio of the ferric chloride hydrate to the modified porous microspheres is 0.5-10: 1; the mass ratio of the ferrous chloride hydrate to the modified porous microspheres is 0.5-10: 1; the mass ratio of the reducing agent to the ferric chloride hydrate is 0.1-10: 1; the mass ratio of the surface functional group compound to the modified porous microspheres is 0.5-10: 1.
6. the novel preparation method of the functionalized porous magnetic microsphere according to claim 5, wherein the surface functional group compound is one of citric acid, polyethylene glycol and oleic acid; the particle size of the surface functionalized magnetic nanoparticles is 5-200 nanometers.
7. The novel preparation method of the functionalized porous magnetic microsphere according to claim 1, wherein the mass ratio of the modified porous microsphere to the surface functionalized magnetic nanoparticles in the step (4) is 1: 1 to 10.
8. The novel preparation method of the functionalized porous magnetic microsphere according to claim 1, wherein the pH of the mixed solution is adjusted to 2.0-9.0 in the step (4).
9. The novel method for preparing functionalized porous magnetic microspheres according to claim 1, wherein the seed microspheres in step (1) are one of polystyrene microspheres, polyglycidyl methacrylate microspheres, polymethyl methacrylate microspheres, polyacrylic acid microspheres, agarose microspheres, dextran microspheres, and chitosan microspheres; the preparation method of the seed microspheres in the step (1) is one of a dispersion polymerization method, an emulsion polymerization method, a soap-free emulsion polymerization method and a miniemulsion polymerization method; the particle size of the seed microspheres in the step (1) is 0.1-5 microns.
10. The novel preparation method of the functionalized porous magnetic microsphere according to claim 1, wherein the functional monomer 2 in the step (5) is one of acrylic acid, methacrylic acid, glycidyl methacrylate, methyl acrylate and ethyl acrylate; in the step (5), the mass ratio of the functional monomer 2 to the porous magnetic microspheres is 1-10: 1; the mass ratio of the allyl glycidyl ether to the porous magnetic microspheres in the step (5) is 1-10: 1.
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| CN114106254A (en) * | 2021-11-25 | 2022-03-01 | 东南大学 | Method for preparing functionalized magnetic polymer microspheres by miniemulsion polymerization method using porous microspheres as templates |
| CN114113287A (en) * | 2022-01-25 | 2022-03-01 | 北京青莲百奥生物科技有限公司 | Serum protein preparation method and serum proteome mass spectrum detection method |
| CN114539600A (en) * | 2022-03-11 | 2022-05-27 | 苏州华度生物科技有限公司 | High-pressure-resistance three-level structured agarose microsphere and preparation method thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114106254A (en) * | 2021-11-25 | 2022-03-01 | 东南大学 | Method for preparing functionalized magnetic polymer microspheres by miniemulsion polymerization method using porous microspheres as templates |
| CN114106254B (en) * | 2021-11-25 | 2023-10-03 | 东南大学 | Method for preparing functionalized magnetic polymer microsphere by miniemulsion polymerization method using porous microsphere as template |
| CN114113287A (en) * | 2022-01-25 | 2022-03-01 | 北京青莲百奥生物科技有限公司 | Serum protein preparation method and serum proteome mass spectrum detection method |
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